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Trinity College Dublin

Personal Information
College Photo Name Khan, Amir Rafiq
Main Department Biochemistry
College Title Assistant Professor
College Tel +353 1 896 3868
Awards and Honours
Award Date
Research Grant - SFI Frontiers Programme 2005
Cyril M. Kay Book Prize in Biochemistry University of Alberta 1995
Studentship, Medical Research Council of Canada 1996
Student Travel Award, American Crystallographic Association St. Louis, MI 1997
Finn Wold Travel Award, Eleventh Symposium of the Protein Society, Boston, MA 1997
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Description of Research Interests
The experimental goal is determination of structures of Rabs with their effector proteins by X-ray crystallography. The first project will involve Rab6, which regulates the forward and retrograde transport pathways at the level of Golgi membranes. The downstream effects of Rab6 are mediated by Rab6IP1, a 1263-residue Rab6IP1 that contains several novel domains for which there is no structural information in the Protein Data Bank. The second project involves Rab11, which is involved in endocytic recycling processes, as well as endosome-to-Golgi trafficking. One of its effectors is FIP2, which belongs to a family of proteins that contain a conserved C-terminal Rab-binding domain. The structures of these effectors may have novel folds, and the complexes with their respective Rabs are likely to demonstrate novel modes of interaction. In addition, the structure of the complex will enable a generalization of the mechanism of Rab family-mediated signaling, since the domains observed in Rab6IP1 are also found in a variety of other mammalian proteins.
Research Interests
Research Projects
Project title X-ray Crystallographic Studies of Poxvirus-Mediated Antagonism of TLR signaling
Summary Toll-like receptors (TLRs) are essential components of innate immunity against bacterial and viral pathogens. The ten TLRs in humans recognize broad types of pathogen associated molecular patterns (PAMPs) including nucleic acids and lipopolysaccharides. The signaling cascade is initiated by their intracellular Toll-like/interleukin-1 receptor (TIR) domains which oligomerize and recruit TIR-containing adaptor proteins such as MyD88 to mediate downstream events. Viruses often attenuate immune responses, and recently, vaccinia virus proteins A46R, A52R and K7R have been shown to antagonize TLR signaling pathways. Interestingly, A46R contains a putative TIR domain that binds to MyD88 and blocks TLR activation, in contrast to the TIR domains of TLRs which promote the signaling cascade. The project described here will involve X-ray crystallographic studies of poxvirus proteins A46R, A52R and K7R alone and in complex with their cellular targets in order to understand the molecular basis for antagonism of TLR signaling.
Funding Agency Science Foundation Ireland
Programme SFI Frontiers Programme
Type of Project
Date from 1/10/2005
Date to 31/9/2008
Person Months 72

Publications and Other Research Outputs
Peer Reviewed
Fernandes, H., Franklin, E., Jollivet, F., Bliedtner, K., Khan, A.R., Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1., PloS one, 7, (4), 2012, pe35637
Notes: [ PubMed ID: 22558185]
TARA - Full Text  DOI
Shun-ichiro Oda, Martina Schroder, Amir R. Khan, Structural Basis for Targeting of Human RNA Helicase DDX3 by Poxvirus Protein K7, Structure (Cell Press), 17, 2009, p1528 - 1537
Jagoe WN, Lindsay AJ, Read RJ, McCoy AJ, McCaffrey MW & Khan AR, Crystal structure of Rab11 in complex with Rab11 Family Interacting Protein 2, Structure (Cell Press), 14, (8), 2006, p1273 - 1283
Notes: [PMID: 16905101 ]
Chen M, Stafford W, Diedrich G, Khan AR and Bouvier M, A characterization of the lumenal region of human tapasin reveals the presence of two structural domains., Biochemistry, 41, (49), 2002, p14539 - 14545
Notes: [PMID: 12463753]
Khan AR, Parrish JC, Fraser ME, Smith WW, Bartlett PA & James MNG, Lowering the entropic barrier for binding conformationally flexible inhibitors to enzymes. , Biochemistry, 37, (48), 1998, p16839 - 16845
Notes: [PMID: 9836576 ]
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Last Updated:17-SEP-2014